Neuroscience, with its offshoots in psychopharmacology, is among the fastest-growing areas of basic medical science. The truism, "If you don't keep up, you will be left behind," is particularly applicable to the field of antidepressant therapy. Five new anti-depressant medications have been introduced during the past 3 years, and many others in the pipeline will soon be available.

In contrast to the first generation of tricyclic antidepressant agents, when each new agent that emerged was merely a clone of the last, recently introduced antidepressants and those in development represent unique compounds that vary in their pharmacologic activity, pharmacokinetic characteristics, and receptor profiles. In general, these newer agents tend to be better tolerated than the tricyclic antidepressants, so it behooves physicians who are treating depressed patients to become familiar with them, keeping in mind that no single antidepressant drug is best for every patient. Only by becoming familiar with the whole array of antidepressant agents can physicians appropriately individualize the treatment of depression to best suit the patient's specific needs. Drugs commonly used in the treatment of depression are listed in table 1.

Principles of antidepressant drug selection: Efficacy

In general, all the available anti-depressants are equally effective for treating depression when they are administered in appropriate doses and for a sufficient length of time. Of particular interest in the treatment of elderly depression are several recent studies in which the efficacy and safety of the newer selective serotonin reuptake inhibitors (SSRIs) have been evaluated in late-life depression (table 2).

Paroxetine. In five controlled trials, paroxetine has been compared with other classes of antidepressants in treating late-life depression.[1-5] Overall, the results of these studies showed that paroxetine in doses of 20 to 40 mg was as effective as the comparator agents amitriptyline, mianserin, clomipramine, and doxepin. In a sixth study by Schone and Ludwig,[6] paroxetine was directly compared to fluoxetine in 106 elderly depressed patients. At week 6, the two drugs produced similar reductions in the Hamilton Depression Scale total score. However, at week 3, the mean score on this scale was significantly lower in patients who received paroxetine [ILLUSTRATION FOR FIGURE 1 OMITTED].

Evaluation of the safety data from the studies of paroxetine in late-life depression showed its improved tolerability vs the tricyclics, especially with regard to sedation, cardiovascular toxicity, and postural hypotension. In a head-to-head trial comparing paroxetine and amitriptyline, the total incidence of adverse effects was lower in depressed patients who took paroxetine (34% vs 63%).[3] In particular, the incidence of anticholinergic side effects was lower in paroxetine-treated patients (7% vs 25%). Demographic analysis of the database from paroxetine worldwide clinical trials demonstrated this SSRI to be as well tolerated in the elderly as in younger patients.[7]

Fluoxetine. In addition to the study by Schone and Ludwig,[6] there have been two other published reports on the use of fluoxetine for treatment of late-life depression.[8,9] Feighner et al[8] compared fluoxetine with doxepin, amitriptyline, and imipramine. The antidepressant responses achieved were similar with all agents, but fluoxetine proved to be better tolerated than the tricyclics. Overall, the fluoxetine-treated group had significantly fewer dropouts (45% of the fluoxetine group vs 55% of the tricyclic group). Nausea was reported by 23.5% and nervousness by 21.3% of fluoxetine-treated patients, compared with 13.7% and 9.9% of tricyclic-treated patients, respectively. However, 57.3% of patients who received a tricyclic reported [TABULAR DATA FOR TABLE 1 OMITTED] [TABULAR DATA FOR TABLE 2 OMITTED] dry mouth and 29.0% reported drowsiness, compared with 20.6% and 11.8% of fluoxetine-treated patients, respectively. Evans noted that fluoxetine treatment of physically ill, geriatric depressed patients reduced mortality and led to an improved quality of life.[9]

Sertraline. The efficacy of sertraline in late-life depression has been evaluated in a study by Cohn et al.[10] In this investigation, improvements in several rating instruments showed sertraline to be as effective as amitriptyline. The greater tolerability of sertraline was evidenced by the higher proportion of amitriptyline patients who withdrew from the study because of drug-related side effects (35%) compared with sertraline patients (28%). …

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